Transcutaneously implantable element

ABSTRACT

A transcutaneously implantable element in which at least a portion thereof in contact with the cutaneous tissue of a living body is composed of a ceramic material comprising, as the main raw material, at least one member selected from the group consisting of hydroxyapatite, tricalcium phosphate, and tetracalcium phosphate, and which comprises (a) an electrically conductive member for electrically connecting the interior and exterior of the living body to each other or (b) a through hole for mechanically connecting the interior and exterior of the living body to each other. 
     This transcutaneously element can be semipermanently and safely used in a living body without causing any desirable bacterial infection, bleeding, and background noise.

This application is a continuation, of application Ser. No. 07/470,438,filed Jan. 24, 1990, now abandoned which is a continuation of U.S. Ser.No. 07/333,876, filed Apr. 3, 1989, now abandoned, which is acontinuation of U.S. Ser. No. 07/000,841, filed Mar. 30, 1987, nowabandoned, which is a divisional of U.S. Ser. No. 06/917,247, filed Oct.7, 1986, now abandoned, which is a continuation of U.S. Ser. No.06/592,436, filed Mar. 22, 1984, now abandoned.

BACKGROUND OF THE INVENTION

1. Field cf the Invention

The present invention relates to a transcutaneously implantable elementin which at least a portion thereof in contact with a cutaneous tissueis composed of a ceramic material comprising, as the main raw material,at least one member selected from the group consisting ofhydroxyapatite, tricalcium phosphate, and tetracalcium phosphate.

2. Description of the Prior Art

Transcutaneously implantable elements such as a percutaneous electrodeconnecter or a cannula are used as an electrical terminal for collectingbiological information such as blood pressure, flow rate of blood,temperature, and electrocardiosignals, or as a port for taking andinjecting blood through the through hole thereof, for example, as a portfor effecting transfusion, injection of liquid medicines, or artificialkidney dialysis. When these transcutaneously implantable elements areused, one end of the element is placed on the skin of a living body andthe other end thereof is buried under the skin. Conventionaltranscutaneously implantable elements already proposed are mainlycomposed of a so-called bioinactive material, for example, a siliconerubber or a fluorine-contained resin.

However, strictly speaking, these transcutaneously implantable elementsare only extraneous substances to a living body, and a portion of theliving body in which the element is mounted is in a traumatized state.Therefore, bacterial infection may be caused from the interstice betweenthat portion and the element. Accordingly, these transcutaneouslyimplantable elements cannot possibly withstand a long period of service.Furthermore, the transcutaneously implantable elements involve problemsin that since they cannot be firmly implanted in the living body,bleeding may occur due to, for example, shaking, and since noise such asa so-called artefact cannot be eliminated when bioelectrical signals,for example, electrocardiosignals, are collected, bioinformation cannotbe stably gathered. Therefore, the transcutaneously implantable elementshave not been widely accepted

For example, with a so-called drug delivery system for an artificialpancreas or the like (see Kraus Heylman, "Therapeutic Systems" publishedby Georg Thieme Publishers, 1978) recently developed rapidly, theproblems of the injection route and the infinitesimal quantityquantitative injection of drugs such as insulin have not been solved asyet (Medical Instrument Society Journal, Vol. 53, No. 2, 1973, infra p.90). Therefore, there is now an increasing demand for a transcutaneouslyimplantable element which can be semi-permanently and safely used as aninjection inlet for drugs.

On the other hand, as the excellent bio-compatibility and bone-derivingability of sintered bodies of hydroxyapatite, tricalcium phosphate orthe like have been clarified recently, the utilization of these sintersas an artificial dental root or an artificial bone has been proposed andpractically effected. However, the physiological reactivity of thesinters to the cutaneous tissue of a living body has not been solved inthe prior art.

SUMMARY OF THE INVENTION

The invention of the instant application resides in the transuctaneouslyimplantable element in which at least a portion thereof in contact witha cutaneous tissue of a living body is composed of a ceramic materialcomprising, as the main raw ingredient, at least one member selectedfrom the group consisting of hydroxyapatite, tricalcium phosphate, andtetracalcium phosphate and which comprises an electrically conductivemember for electrically connecting the interior and exterior of theliving body to each other.

Other objects and advantages of the present invention will be apparentfrom the description set forth hereinbelow.

In accordance with the present invention, there is provided atranscutaneously implantable element in which at least a portion thereofin contact with the cutaneous tissue of a living body is composed of aceramic material comprising, as the main raw material, at least onemember selected from the group consisting of hydroxyapatite, tricalciumphosphate, and tetracalcium phosphate, and which comprises (a) anelectrically conductive member for electrically connecting the interiorand exterior of the living body to each other or (b) a through hole formechanically connecting the interior and exterior of the living body toeach other.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention will now be better understood from the followingdescriptions presented in connection with the accompanying drawings inwhich:

FIGS. 1 to 8 are schematic cross sectional views of the transcutaneouslyimplantable elements I, II, III, IV, V, VI, VII, and VIII according tothe present invention.

The material composition, method of preparation, shape, structure, andembodiment of use of the transcutaneously implantable element, plug orconduit of the present invention will be described in detail.

Material Composition and Preparation

The term "ceramic material" as used herein means a sinter comprising, asthe main raw material, at least one member selected from the groupconsisting of hydroxyapatite, tricalcium phosphate, and tetracalciumphosphate, and a coated material comprising a substrate, for example, ametal or a ceramic, flame sprayed- or sinter-coated with theabove-mentioned sinter The ceramic material may contain variousadditives such as MgO, Na₂ O, K₂ O, CaF₂, Al₂ O₃, SiO₂, CaO, Fe₂ O₃,MnO, MnO₂, ZnO, C, SrO, PbO, BaO, TiO₂, and ZrO₂ order to enhance thesinterability, strength, and porosity thereof, and other properties.

The term "hydroxyapatite" as used herein includes a pure hydroxyapatitewhose chemical composition is represented by the formula Ca₁₀ (PO₄)₆(OH)₂ and a modified hydroxyapatite containing 1% to 10% of a carbonate(CO₃) ion, a fluoride ion or a chloride ion in place of a hydroxyl (OH)ion in the formula Ca₁₀ (PO₄)₆ (OH)₂. The hydroxyapatite may containwell-known additives such as Ca₃ (PO₄)₂, MgO, Na₂ O, K₂ O, CaF₂, Al₂ O₃,SiO₂, CaO, Fe₂ O₃, MnO, MnO₂, ZnO, C, SrO, PbO, BaO, TiO₂, and ZrO₂ inorder to enhance the sinterability, strength, and porosity thereof, andother properties.

Where the hydroxyapatite is used as a composite material with apolymeric material, the polymeric material may be selected from resinshaving a relatively low toxicity, for example, polyethylene,polypropylene, polymethyl methacrylate, polyurethanes, polyesters, ABSresins, fluorine-contained resins, polycarbonates, polysulfone, epoxyresins, silicones, diallyl phthalate resins, and furan resins.

On the other hand, the methods of preparation of the ceramic materialinclude a so-called sintering method in which the raw material issintered singly or on a substrate such as a metal, plastics or ceramicsand vapor deposition methods such as a plasma spray coating method, anion beam deposition method and a vacuum evaporation method in which theraw material is plasma sprayed on a substrate such as a metal orceramics.

For example, the single sintered material is generally obtained bycompress molding a raw material comprising hydroxyapatite, tricalciumphosphate or tetracalcium phosphate in a mold or a rubber press under apressure of approximately 500 to 3,000 kg/cm², to obtain a compacthaving a desired shape, and then subjecting the compact to a sinteringtreatment at a temperature of approximately 700° C. to 1,300° C. Forfurther details of other methods of preparation and the materialcomposition, reference will be made to the following publications:Japanese Unexamined Patent Publication (Kokai) Nos. 51-40400, 52-64199,52-82893, 52-142707, 52-147606, 52-149895, 53-28997, 53-75209,53-111000, 53-118411, 53-144194, 53-110999, 54-94512, 54-158099,55-42240, 55-51751, 55-56062, 55-130854, 55-140756, 56-18864, 56-45814,56-143156, and 56-166843, and Japanese Examined Patent Publication(Kokoku) Nos. 57-40776, 57-40803, and 58-39533.

From the standpoint of joining with the cutaneous tissue of a livingbody, an especially useful sinter for the present invention has arelative density (based on the density of a single crystal ofhydroxyapatite) of 60% to 99.5%, desirably approximately 85% to 95%.Where the transcutaneously implantable element of the present inventionis used as an injection route of a liquid medicine in the drug deliverysystem, as described hereinafter, a portion of the element in contactwith the cutaneous tissue may be provided with a porous member.

The porous members usable for this purpose are those which are able tofunction as a barrier layer against the penetration of the tissue of aliving body into the passage of liquid medicines and the spontaneousdiffusion of the concentration of drugs. Examples of such porous membersare porous resin films such as a porous Teflon film; sintered porousresins which are used as a filter medium or a filter membrane; porousceramics such as sintered porous alumina; porous glass; sintered porousmetals such as sintered platinum; electrochemical diaphrams, such asporcelain diaphram, as used in the electrolytic industry; dialysismembranes; and porous materials consisting of calcium phosphate whichare disclosed in the above-mentioned patent publications. These porousmembers may be in the form of a film, sheet, cylinder or the like,having an appropriate average pore diameter, and may be suitablyselected depending on the intended use.

To ensure that it effectively functions as the barrier layer, it isdesirable that the porous member usually have an average pore diameterof 0.01 μ to 1 mm, preferably 0.5 μto 700 μ. Generally, the average porediameter of the porous member is variable depending on the site to beimplanted, the implantation depth, the molecular weight andconcentration of the drug used, and the form of energy used for the druginjection.

Especially when ultrafiltration membranes for artificial dialysis suchas those made of polymeric materials having a fraction molecular weightof approximately 10,000 to 50,000, for example, regenerated cellulose,polyacrylonitrile, polymethyl methacrylate, cellulose acetate,polycarbonate, polysulfone, and polyamide, or filter or precision filtermembranes having an average pore diameter of approximately 0.5 μ to 100μ, are used as the porous member of the present invention, thesemembranes function fairly satisfactorily as the barrier layer. However,because of their high filtration resistance, it is not always preferableto use mechanical energies such as pressure as the injection energy fordrugs. In this case, the use of electrochemical driving forces such asiontophoresis or electroendosmosis, as described hereinafter, ispreferable. For example, as is well known, electroendosmosis is aphenomenon wherein when an electrical voltage is applied to a porousbody having pores, a liquid is quantitatively migrated to either of acathode and an anode due to the electrochemical properties at theinterface. The transcutaneously implantable element of the presentinvention is also applicable to this type of method. In this case,selection of a liquid medicine and a porous member is carried out aftertaking into account their interfacial electrochemical properties.

Shape and Structure

The shape of the transcutaneously implantable element of the presentinvention is variable, depending on the end use thereof. A typicalexample of the element is described below in detail with reference tothe accompanying drawings.

FIG. 1 is a cross sectional view showing an example of thetranscutaneously implantable element of the present invention. In thedrawing, a transcutaneously implantable element I used as an electricalterminal comprises an element head 2 and an element bottom 3 integrallycombined with each other. Both the head 2 and the bottom 3 are compesedof the ceramic material of the present invention. Within the element 1,there is buried an electrically conductive member 4 such as gold wire,silver wire, platinum wire, alloy wire, and carbon fiber to electricallyconnect the interior of a living body to the exterior thereof. Ifnecessary, one or not less than two holes 5 for suturing are bored inthe bottom 3.

The transcutaneously implantable element 1 having the above-mentionedstructure is implanted in such a manner that the bottom 3 is fixedlyburied under the skin and the upper end of the head 2 is protruded abovethe skin. After this implanting, the element I is used as an electricalterminal for gathering bioelectrical signals or the like, or forconnecting bioelectrically stimulating devices such as a pacemaker.

Similarly, FIG. 2 is a cross sectional view showing an example of thetranscutaneously implantable element of the present invention which isused as a bioplug. The transcutaneously implantable element II has thesame structure as the transcutaneously implantable element I exceptthat, in place of the conductive member 4, a through hole 6 is providedfor connecting the interior of a living body to the exterior thereof. Inthe drawing, the same reference numerals denote the same parts as shownin FIG. 1.

In the other hand, since a desired object can be attained so long as aportion of the transcutaneously implantable element in contact with thecutaneous tissue is composed of the ceramic material of the presentinvention, the transcutaneously implantable element may be of astructure wherein only an essential portion thereof is composed of thesinter and the other portions are composed of other materials such assynthetic resins. Altenatively, the essential portion may be composed ofa coated material consisting of a ceramic material comprising, as themain raw material, at least one member selected from the groupconsisting of hydroxyapatite, tricalcium phosphate, and tetracalciumphosphate, (for examples, see, Japanese Unexamined Patent Publication(Kokai) Nos. 52-82893, 53-28997, 53-75209, 53-118411, and 58-39533).

For example, a metallic microneedle coated with a flame sprayed orsintered layer of hydroxyapatite at the peripheral surface thereof canbe used as the electrically transcutaneously implantable element.

FIG. 3 is a cross sectional view of a transcutaneously implantableelement III in the form of microneedle. The element III comprises ametallic needle 7, such as a gold needle, coated with a coated or flamesprayed layer 8 consisting of the ceramic material of the presentinvention. When this type of element is used, it is implanted merely bypiercing the skin of a patient. Furthermore, the transcutaneouslyimplantable element of the present invention may be used as an inlet fordosing drugs in drug delivery systems, as described hereinafter. In thiscase, transcutaneously implantable elements having the shapes shown inFIGS. 4 through 8 are especially useful.

FIG. 4 is a cross sectional view showing another example of thetranscutaneously implantable element of the present invention. In thedrawing, a transcutaneously implantable element IV used as an inlet forinjecting drugs comprises an element head 2 and an element bottom 3integrally combined with each other. Both the head 2 and the bottom 3are composed of the ceramic material of the present invention. Withinthe head 2, there is provided a cylinder 12 which is made of a metal ora synthetic resin such as a silicone resin and is equipped with amembrane filter for removing bacteria, such as a Millipore Filter®, atthe middle or end portion thereof. A desired drug is injected into aliving body through a through hole 6.

FIG. 5 is a cross sectional view of a transcutaneously implantableelement V in the form of a microtube. The element V comprises a metallictube 9, such as a gold tube, coated with a coating layer 10 consistingof the ceramic material of the present invention at the peripheralsurface thereof. This element is implanted merely by being buried in theskin of a patient.

FIG. 6 is a cross sectional view of a transcutaneously implantableelement VI in the form of a microtube. The element VI comprises ametallic tube 9, such as a gold tube, coated with a sinter coating orflame-sprayed layer 10 consisting of hydroxyapatite at the peripheralsurface thereof and a filter means 14 for removing bacteria having afilter 13 connected to the end of the head. This element is implantedmerely by being buried in the skin of a patient.

Furthermore, to hinder the spontaneous diffusion of drugs as much aspossible, it is possible to provide a portion of the transcutaneouslyimplantable element in contact with the tissue of a living body with abarrier layer, as shown in FIG. 7. In the drawing, a transcutaneouslyimplantable element VII used as an inlet for injecting drugs comprisesan element head 2 and an element bottom 3 integrally combined with eachother, both the head 2 and the bottom 3 being composed of the ceramicmaterial of the present invention, and a cylinder 16 made of a metal ona synthetic resin such as a silicone resin and provided in the head 2and which is provided, at the middle or end portion thereof, with aporous member 15 such as an ultrafiltration member, for example, AmiconPM-30, 0.22 μ millipore membrane filter or a sintered polyethylenefilter having an average pore diameter of 15 μ. A desired drug isinjected into a living body through a through hole 6 of the cylinder 16.

FIG. 8 is a cross sectional view of a transcutaneously implantableelement VIII in the form of a microtube. The element VIII comprises ametallic tube 9, such as a gold tube, coated with a coating orflame-sprayed layer 10 consisting of the ceramic material of the presentinvention, and a porous member 15 consisting of a sintered aluminahaving an average pore size of 3 μ provided in the lower end of the tube9.

A plastic drug reservoir may be integrally joined with the top of thetranscutaneously implantable elements having the shapes shown in FIGS. 4through 8 to provide a drug delivery system.

As is apparent from the foregoing, the transcutaneously implantableelement of the present invention can assume a variety of shapes,structures and sizes, and thus, are not limited to any specific form.

It is evident from the above-mentioned description that thetranscutaneously implantable element of the present invention composedof the ceramic material comprising, as the main raw material, at leastone member selected from the group consisting cf hydroxyapatite,tricalcium phosphate, and tetracalcium phosphate, has an adaptability toa living body and, further, it forms an interface junction with thecutaneous tissue, such as epidermis and dermis, of the living body to bestably implanted in the living body. Therefore, the trancutaneouslyimplantable element of the present invention can be widely used as aterminal for connecting an external electric source to a heartpacemaker, an outlet for blood dialysis, and a terminal for connecting abiowire having sensor elements, for example, an ultrasonic sensorelement, at the tip thereof to an external measuring instrument.Accordingly, the transcutaneously implantable element of the presentinvention is very useful in the fields of diagnosis, therapy, animalexperiments, and the like.

Furthermore, the transcutaneously implantable element having a throughhole has wide application as an inlet for dosing drug in drug deliverysystems. When this element is used as the drug inlet, it is buried andimplanted in the skin of a living body and a tube for feeding a liquidmedicine which is quantitatively driven by means of a micropump or thelike can be connected only to the implanted element.

Now, as an especially useful embodiment of the transcutaneouslyimplantable element of the present invention, there is mentioned its useas an injection inlet for a so-called iontophoresis in which the dosingof a drug is electrochemically driven.

For example, the injection of insulin.HCl into an artificial pancreashas been conventionally effected by using a microquantitative injectionpump. By merely connecting the transcutaneously implantable element tothe positive pole of a direct current source instead of using the pump,it is possible to introduce insulin.cation into a living body veryeasily and stably.

A conventional iontophoresis is applied from the upper surface of theskin. In this case, the cutaneous keratin layer acts exclusively as anelectrical and physical barrier which renders the introduction of arelatively large molecule, e.g., insulin, difficult. Contrary to this,in accordance with the transcutaneously implantable element of thepresent invention, since the cutaneous keratin layer can no longerfunction as the barrier, a remarkable reduction in the impedance andphysical resistance results. Furthermore, quantitative injection orfeedback injection by a glucose sensor can be readily attained bycontrolling the current value (in the case of insulin, usually withinthe range of several μA to several mA when direct current or pulsedirect current is used). That is, where the transcutaneously implantableelement is used in iontophoresis, instead of using a liquid medicineimpregnation technique (generally a water retainable material is usedsuch as a sponge or cotton, or a hydrophilic gel) for conventionaliontophoresis, a conduit for injecting a liquid medicine is connected tothe element to provide a passage for the medicine. A non-barrier memberconsisting of well-known bioelectrodes (for example, Japanese UnexaminedPatent Publication No. 58-10066 or Japanese Patent Application No.56-106935) is attached on another site of the skin. A direct current isthen passed between the working electrode and the counter electrode (ifan ionic drug is a cation, the working electrode is an anode).

For further details of the iontophoresis itself, refer to theabove-mentioned patent publications.

EXAMPLES

The present invention will be illustrated by, but is by no means limitedto, the following examples.

EXAMPLE I 1. Preparation of a transcutaneously implantable element

0.5 mole/l of calcium hydroxide and 0.3 mole/l of a phosphorous acidsolution were gradually mixed dropwise to react these materials at atemperature of 37° C. for one day. The resultant reaction mixture wasfiltered and dried to obtain hydroxyapatite powder. 3 g of the syntheticpowder was filled in a mold having an inner diameter of 15 mm and moldedtogether with a fine gold wire having a diameter of 0.05 mm, under apressure of 800 kg/cm², to obtain a compact having a bulk density of 1.6g/cm³. This compact was cut and processed by using a lathe and a dentaldiamond bar to provide an element head (FIG. 1).

Similarly, 4.5 g of the above-synthesized powder was filled in a moldhaving an inner diameter of 30 mm together with a gold wire, to obtain acompact specimen, after which molding, cutting, and processing wereeffected to obtain an element bottom (FIG. 1). The gold wires of thesecompact specimens were then joined together, and a gelatinous apatitepowder which was thoroughly kneaded with water in a mortar was appliedto the junction of the compacts to bond them to each other. Theresultant composite product was subjected to a sintering treatment at atemperature of 1,250° C. for 1 hour, to obtain a transcutaneouslyimplantable element, as shown in FIG. 1, having a compressive strengthof 5,000 kg/cm², a bending strength of 1,200 kg/cm², a relative densityof 95%.

In the resultant transcutaneously implantable element, the elementbottom had a diameter of 24 mm and a thickness of 3 mm, and the neck ofthe element head had an average diameter of 6 mm.

Further, when the sintering temperature was 1,100° C., the resultantsinter had a relative density of 85%, a compressive strength of 3,000kg/cm², and a bending strength of 700 kg/cm².

2. Animal experiment

The above-mentioned transcutaneously implantable element was buried inthe side abdominal skin of a crossbred adult dog and variations in theburied site over a period of time were observed. About two weeks afterthe operation, it was found that the element was tightly combined andjoined with the skin tissue at the bottom and neck portions thereof toan extent wherein it could not be forcibly separated from the skintissue. Even after the lapse of one year, no abnormal phenomenon such asinflammation reaction could be observed with the naked eye.

A conventional histological examination also revealed the absence of anyinflammatory cells.

On the other hand, when a transcutaneously implantable element of thesame shape made of a silicone rubber was buried as a control, even fourweeks after the operation, joining of the element with the skin tissuecould not be observed and inflammatory rubefaction had already appeared.Two months after the operation, the inflammation had worsened and hadbegan to suppurate, and three months after the operation, the elementbecame detached from the skin.

EXAMPLE II

A sinter in the form of a small column with a diameter of 3 mm,containing a gold wire 0.05 mm in diameter, was prepared in a mannersimilar to that described in Example I, except that a powdery mixture ofthe above-mentioned hydroxyapatite powder and, as additives 7% of Ca₃(PO₄)₂, 0.8% of MgO, 1.8% of Na₂ O, 0.2% of K₂ O, and 0.2% of CaF₂ wereused as the starting material. The resultant sinter was subjected to anabrasion treatment using an abrasive to obtain a microneedle-likeelement having the shape shown in FIG. 3.

The sinter portion of the element had a length of 10 mm and a maximumdiameter of 1 mm.

Then, a predetermined number of the microneedlelike elements werepierced and buried in the thorax of an adult dog, in such a manner thattheir tips were located under the skin. Approximately three weeks afterthe elements were buried, the elements were completely joined with thecutaneous tissue and implanted therein.

The gold wire of the element was then connected to an electrocardiographto effect measurement. As a result, a very clear electrocardiogram fromwhich any influence due to cutaneous impedance or artefact wascompletely eliminated was obtained.

EXAMPLE III 1. Preparation of a transcutaneously implantable element

Synthetic powder of tricalcium phosphate was filled in a mold and wasmolded together with a fine gold wire having a diameter of 0.05 mm undera pressure of 800 kg/cm² to obtain a compact having a bulk density of1.6 g/cm³. The resultant compact was cut and processed by using a latheand a dental diamond bar to provide an element head (FIG. 1). Similarly,the above-mentioned synthetic powder was filled in a mold together witha gold wire, to obtain a compact, after which compression molding,cutting, and processing were effected to obtain an element bottom (FIG.1). The gold wires of these compacts were then joined together, and agelatinous apatite powder which was thoroughly kneaded with water in amortar was applied to the junction of the compacts to bond them to eachother. The resultant composite product was subjected to a sinteringtreatment at a temperature of 1,200° C. for 1 hour to obtain atranscutaneously implantable element, as shown in FIG. 1, having acompression strength of 4,300 kg/cm², a bending strength of 1,000kg/cm², and a relative density of 93%.

In the resultant transcutaneously implantable element, the elementbottom had a diameter of 20 mm and a thickness of 2 mm and the neck ofthe element head had a diameter of 5 mm.

2. Animal experiment

The above-mentioned transcutaneously implantable element was buried inthe side abdominal skin of a crossbred adult dog and variations in theburied site over a period of time were observed. About two weeks afterthe operation, it was found that the element was tightly combined andjoined with the skin tissue at the bottom and neck portions thereof, toan extent that it could not be forcibly separated from the skin tissue.Even after the lapse of one year, no abnormal phenomenon such asinflammation reaction could be observed with the naked eye.

A conventional histological examination also revealed the absence of anyinflammatory cells.

On the other hand, when a transcutaneously implantable element of thesame shape made of a silicone rubber was buried as a control, even fourweeks after the operation, no joining of the element with the skintissue could be observed and inflammatory rubefaction had alreadyappeared. Two months after the operation, the inflammable had worsenedand began to suppurate, and three months after the operation, theelement became detached from the skin.

EXAMPLE IV

A sinter in the form of a small column with a diameter of 3 mm,containing a gold tube having a diameter of 1 mm, was prepared in amanner similar to that described in Example III, except that a powderymixture of the above-mentioned tricalcium phosphate powder and, asadditives, 0.8% of MgO, 1.8% of Na₂ O, 0.2% of K₂ O, and 0.2% of CaF₂were used as the starting material. The resultant sinter was subjectedto an abrasion treatment using an abrasive to obtain an element in theform of a microtube having the shape shown in FIG. 5.

The sinter portion cf the element had a length of 8 mm and an outerdiameter of 2 mm.

The element was then pierced and buried in the thorax of an adult dog sothat the bottom thereof was located under the skin. Approximately threeweeks after the element was buried, the element was completely joinedwith the cutaneous tissue and implanted therein.

Next, the end of the element head was connected to a conduit filled withphysiological saline to measure the DC resistance (an electrode for anelectrocardiogram, Lectroad®, manufactured by Advance Electrode Co.,Ltd. was attached to another portion of the shaved thorax as the counterelectrode). As a result, a resistance value of 3.6 kΩ. was obtained,confirming a remarkable reduction in the resistance when compared to theusual cutaneous resistance through the keratin layer of approximately100 kΩ.

EXAMPLE V

70% by weight of tricalcium phosphate and 30% by weight of tetracalciumphosphate were mixed. The resultant mixture was molded into an elementhead and an element bottom, and the head and bottom were joined togetherin a manner similar to that described in Example 1. The resultantcomposite product was subjected to a sintering treatment at atemperature of 1,250° C. for 1 hour to obtain a transcutaneouslyimplantable element as shown in FIG. 2.

The same animal experiment as in Example 1 was carried out using theresultant above transcutaneously implantable element. Almost the sameresults as those obtained in Example IV were obtained.

EXAMPLE VI

A coating layer of tricalcium phosphate was formed on the surface of acore consisting of a fine gold wire of 0.05 mm inner diameter by using aplasma spray coating method. The coated core was sintered at atemperature of 1,200° C. for 10 minutes, and the resultant sinter wasabrasion-treated with an abrasive to obtain a transcutaneouslyimplantable element in the form of a microneedle as shown in FIG. 3.

The same animal experiment as in Example II was then carried out usingthe resultant above element. Substantially the same results wereobtained as in Example II.

EXAMPLE VII

A coating layer of tetracalcium phosphate was formed on the surface of acore consisting of a fine gold wire of 0.05 mm inner diameter by using,as the starting material, a powdery mixture of tetracalcium phosphatepowder and, as additives, 7% of Ca₃ (PO₄)₂, 0.8% of MgO, 1.8% of Na₂ O,0.2% of K₂ O, and 0.2% of CaF₂, in the same manner as that of ExampleVI. After the coated core was sintered, it was abrasiontreated with anabrasive to obtain a microneedle-like element having the shape shown inFIG. 3.

When the same animal experiment as in Example VI was carried out, usingthe resultant above element, substantially the same results wereobtained as in Example VI.

EXAMPLE VIII

Synthetic hydroxyapatite powder obtained in the same manner as inExample I was filled in a mold and compression molded under a pressureof 800 kg/cm², to obtain a compact having a through hole 2 mm indiameter and having a bulk density of 1.6 g/cm³. The compact specimenwas cut and processed by using a lathe and a dental diamond bar toobtain an element head (FIG. 1). Similarly, the above-mentionedsynthetic powder was filled in a mold and was molded, to obtain acompact, after which cutting and processing were carried out to obtainan element bottom (FIG. 1). The through holes of these compacts werejoined together and a gelatinous apatite powder which was thoroughlykneaded with water in a mortar was applied to the junctions of thecompacts to bond them to each other. The resultant composite product wassubjected to a sintering treatment at a temperature of 1,250° C. for 1hour to obtain a transcutaneously implantable element, as shown in FIG.4, having a compressive strength of 5,000 kg/cm², a bending strength of1,200 kg/cm², and a relative density of 95%.

In the resultant transcutaneously implantable element, the elementbottom had a diameter of 5.4 mm and a thickness of 2 mm, and the neck ofthe element head had an outer diameter of 4 mm and an inner diameter of2 mm.

Furthermore, when the sintering temperature was 1,100° C., the resultantsinter had a relative density of 85%, a compressive strength of 3,000kg/cm², and a bending strength of 700 kg/cm². Finally, a synthetic resincylinder equipped with a filter means for removing bacteria was providedin the element, as shown in FIG. 4, to provide a sample.

2. Animal experiment

The above-mentioned transcutaneously implantable element was buried inthe side abdominal skin of a crossbred adult dog and variations in theburied site over a period of time were observed. About two weeks afterthe operation, it was found that the element was tightly combined andjoined with the skin tissue at the bottom and neck portions thereof, toan extent that it could not be forcibly separated from the skin tissue.Even after the lapse of one year, no abnormal phenomenon such asinflamation reaction could be observed with the naked eye.

A conventional histological examination also revealed the absence of anyinflamed cells.

On the other hand, when a transcutaneously implantable element of thesame shape made of a silicone rubber was buried as a control, even fourweeks after the operation, no joining of the element with the skintissue could be observed and inflammatory rubefaction had alreadyappeared. Two months after the operation, the inflammation had worsenedand had begun to suppurate, and three months after the operation, theelement became detached from the skin.

EXAMPLE IX

Hydroxyapatite synthesized in the same manner as in Example VIII wasmixed with Ca₃ (PO₄)₂, MgO, Na₂ O, K₂ O, and CaF₂ in the sameproportions as in Example II. A sinter in the form of a small columnwith an cuter diameter of 3 mm containing a gold tube 1 mm in diameterwas prepared from the resultant mixture in a manner similar to thatdescribed in Example III. The resultant sinter was abrasion treated withan abrasion to obtain a microtubular element having the shape shown inFIG. 5.

The sinter portion of the element had a length of 8 mm and an outerdiameter of 2 mm.

A filter means for removing bacteria was then connected to the element,as shown in FIG. 6. This element was pierced and buried in the thorax ofan adult dog so that the bottom thereof was located under the skin.About three weeks after the element was buried, the element wascompletely joined with the cutaneous tissue and implanted therein

Next, the end of the element head was connected to a conduit filled withphysiological saline to measure the DC resistance (an electrode for anelectrocardiogram, Lectroad®, manufactured by Advance Electrode Co.,Ltd. was attached to another portion of the shaved thorax as anon-barrier member). As a result, a resistance value of 1.7 kΩ wasobtained, confirming a remarkable reduction in resistance when comparedwith the usual cutaneous resistance through the keratin layer ofapproximately 100 kΩ.

EXAMPLE X

A synthetic resin cylinder equipped with a porous member (a Teflon resinfilm having an average pore diameter of 4 μ) was provided in thetranscutaneously implantable element prepared in Example VIII, as shownin FIG. 7, so as to provide a sample.

The sample was buried in the side abdominal skin of a crossbred adultdog and variations in the buried site over a period of time wereobserved. An excellent adaptability of the sample to the cutaneoustissue was found, as in Example IX.

EXAMPLE XI

A porous member made of an alumina sinter having an average pore size of50 μ was connected to the transcutaneously implantable element preparedin Example IX, as shown in FIG. 8. The resultant element was pierced andburied in the thorax of an adult dog so that the bottom thereof waslocated under the skin. Approximately three weeks after the element wasburied, the element was completely joined with the cutaneous tissue andimplanted therein.

The end of the element head was then connected to a conduit filled withphysiological saline to measure the DC resistance (an electrode for anelectrocardiogram, Lectroad®, manufactured by Advance Electrode Co.,Ltd. was attached to another portion of the shaved thorax as anon-barrier member). As a result, a resistance value of 3.8 kΩ wasobtained, confirming a remarkable reduction in resistance when comparedto the usual cutaneous resistance through the keratin layer ofapproximately 100 kΩ.

We claim:
 1. A transcutaneously implantable element in which at least aportion thereof in contact with the cutaneous tissue of a living body iscomposed of a ceramic material comprising, as the main raw material, atleast one member selected from the group consisting of hydroxyapatite,tricalcium phosphate, and tetracalcium phosphate, and which comprises anelectrically conductive member for electrically connecting the interiorand exterior of the living body to each other.
 2. The element of claim 1in which said element is formed by sintering a compact of said ceramicmaterial.
 3. The element of claim 1 in which said element is formed bycoating said ceramic material on the surface of a substrate.
 4. Theelement of claim 1 in which said element is formed by vapor depositionof said ceramic material on the surface of a substrate.